CATIONIC AND SECRETORY EFFECTS OF GLIMEPIRIDE AND GLIBENCLAMIDE IN PERIFUSED RAT ISLETS

The effects of glimepiride and glibenclamide upon Rb-86 outflow, Ca-45 outflow and insulin release were examined in rat islets Perifused at low (zero to 2.8 mM) or close-to-normal (8.3 mM) D-glucose concentrations. At the low hexose concentrations, a marked and not reversible decrease in Rb-86 outflow contrasted with a rapid and reversible increase in Ca-45 outflow. The latter increase was abolished in the absence of extracellular Ca2+, and was not associated with any pronounced stimulation of insulin release. Inversely, in the presence of 8.3 mM D-glucose, a comparable increase in Ca-45 efflux now coincided with an increase in Rb-86 efflux and a marked and not reversible stimulation of insulin release. Whether in terms of the time course or glucose dependency of the cationic and secretory responses, a coupled increase in both Ca-40 inflow and Ca-45 outflow thus coincided with either negative or positive changes in Rb-86 outflow and either minimal or marked changes in insulin output. Such dissociated behaviours suggest that the insulinotropic action of hypoglycemic sulfonylureas is not necessarily attributable solely to a primary decrease in K+ conductance.